This proposal is to renew funding for the Smooth Muscle Plasticity Center of Biomedical Research Excellence (COBRE) at the University of Nevada, Reno (UNR). The COBRE has expanded the research infrastructure and helped to develop the careers of several highly promising young investigators. The center has a strong thematic focus in smooth muscle biology. The COBRE consists of 5 projects that are investigating various aspects of smooth muscle plasticity. Project 1: Correlation between structural and motor defects in diabetic gastroparesis to be headed by Dr. Grant Hennig;Project 2: Phopholamban and CaM Kinase II in smooth muscle plasticity to be headed by Dr. Brian Perrino;Project 3: An in vitro model system for determining regulatory mechanisms for smooth muscle mechanics to be led by Dr. Josh Baker;Project 4: Smooth muscle hypertrophy regulated by microRNAs and their target genes to be headed by Dr. Seungil Ro;Project 5: Stretch-dependent potassium channel regulation in overactive bladder to be led by Dr. Sang Don Koh. The projects are supported by Core lab facilities: Core A: Administration and faculty development;Core B: Molecular expression and transgenics;Core C: Protein expression and cell morphology;and Core D: Dynamic imaging. The COBRE will be administered by: i) the Central COBRE Administration consisting of the PI and Co-PI, administrative assistant and computer specialist;ii) an Internal Advisory Committee (lAC) with mentors for each project leader;and iii) an External Advisory Committee (EAC) consisting of leaders in smooth muscle biology. Mentors in the lAC are distinguished scientists with productive careers in biomedical research. The lAC establishes milestones for career development, performs formative and summative evaluation of progress toward milestones, and assists the Project Leaders in the central goal of developing independent funding and sustainable research careers. The COBRE is led by Drs. Kenton Sanders and Christine Cremo as PI and Co-PI, respectively. The PI and Co-PI are highly qualified, with many years of administrative and scientific experience in the thematic focus of the COBRE. PUBLIC HEALTH RELEVANCE (provided by applicant): Smooth muscles are unique among muscle lineages because they change phenotype in response to a variety of stimuli. Pathophysiological conditions result from phenotypic changes in smooth muscle tissues, but the cause and consequences of remodeling and hypertrophy are not well understood. Several disease models of smooth muscles will be used to learn how phenotypic change contributes to pathophysiology.